Oxathianes, substituted

The synthesis of the 2-acyloxathianes 3 makes use of the fact that for stereoelectronic reasons1, electrophilic attack on conformationally locked 2-lithiated oxathianes 1 leads exclusively to equatorially substituted products 2. A subsequent oxidation step completes the synthesis. 

Ab initio calculations at the MP2 level of theory of a collection of substituted 1,3-dioxanes, 1,3-oxathianes, and 1,3-dithianes have been employed to study both the position of the conformational equilibria and the validity of the Perlin effect <2005T7349>. The 7h,c coupling constant proved to be a valuable tool in conformational analysis both twist conformers, in addition to the chair and alternative chair forms, could be readily identified simply by comparing experimental Vh,c coupling constants to the corresponding calculated values in the particular forms. In addition, the Perlin and reversed-Perlin effects of the C2-H fragments, c in 1,3-dioxanes,... 

Also, the reaction pathways of the Corey-Chaykovsky epoxidation reaction have been compared quantum-chemically <1999JOC4596>. As models for one transition state, 1,3-oxathiane compounds such as 52, suitably substituted to allow comparison with experiment (Equation 3), were calculated and these predicted both the absolute stereochemistry of the main product 53 and the distribution of the other stereoisomers, as supported by experimental results. Thus, this theoretical study was able to identify the transition state which proved to be responsible for the stereoselectivity of the catalytic Corey-Chaykovsky epoxidation reaction. 

The publication of X-ray structures from 1996 onward has continued and altogether ca. 30 structures have been published. Bond and dihedral angles for the preferred conformation of the 1,3-oxathiane rings are determined by the ring fusion and/or attached substituents thus, published structures were classified as either monocyclic (mono), spiro-substituted (spiro), bicyclic (bi), or tricyclic (tri). For each of the four groups, derivatives were found and a comparison of the experimental bond lengths for the 1,3-oxathiane ring system with representatives of the different classes are... 

Grosu and co-workers also studied the complex configurational and conformational aspects of the unique stereochemistry of substituted spiro-l,3-oxathiane derivatives 100-102 by NMR spectroscopy <2001T8751>. 

A [4-f2] cycloaddition was the key step in the synthesis of substituted dihydrothiopyrans from 2-alkenyl-l,3-oxathianes and an alkene. The reaction was mediated by a Lewis acid. It is assumed that the Lewis acid attacks the oxygen of the heterocycle which upon ring opening gives the highly reactive cationic heterodiene which reacts with alkenes to the thiopyrans in 31-88% yield (Scheme 75) <2000TL371>. 

Various 2-functionalized-l,3-oxathianes have been prepared from 1,3-thioalcohols by a combined SNV/Michael addition sequence using (Z)-l,2-bis-phenylsulfonylethylene (BPSE) as Michael acceptor. The yields were in the range of 72-90% for aliphatic 1,3-thioalcohols and somewhat lower for 2-hydroxymethyl-substituted aromatic thiols (33%) (Equation 90) <2003TL5723>. 

Chiral bis-lithium amide bases have been used for enantiotopic deprotonation of the sulfonium salt of 1,4-oxathiane 86. The anion undergoes an enantioselective thia-Sommelet rearrangement to afford the 3-substituted-1,4-oxathiane 87. Only bis-lithium amide bases were effective, giving products with high diastereoselectivity and with low to moderate enantioselectivity (Equation 13) <2003TL8203>. 

Synthesis of 2,3-dihydro-l,4-dithiin 11 was accomplished from l,3-dithiol-2-one 247 in the presence of dibro-moethane and potassium hydroxide <1998JOG3952>, while reaction of 2,3-dichloro-l,4-dioxane with powdered Zn in hexamethylphosphoramide (HMPA) was used for the synthesis of 1,4-dioxene 10 <1998JPP10067773>. To obtain substituted 1,4-oxathianes, the hydrogenation of the corresponding partially saturated compounds has been employed <2001J(P1)2604>. 

The dichloro compounds 65 derived from l,4-oxathiane-3-carboxanilides 64 yield bicyclic P-lactams on treatment with base through an intramolecular nucleophilic substitution facilitated by the neighbouring sulfur atom <99H(50)713>. 

Carbon-13 shift values of parent heterocycloalkanes [408] collected in Table 4.61 are essentally determined by the heteroatom electronegativity, in analogy to the behavior of open-chain ethers, acetals, thioethers, thioacetals, secondary and tertiary amines. Similarly to cyclopropanes, three-membered heterocycloalkanes (oxirane, thiirane, and azirane derivatives) display outstandingly small carbon-13 shift values due to their particular bonding state. Empirical increment systems based on eq. (4.1) permit shift predictions of alkyl- and phenyl-substituted oxiranes [409] and of methyl-substituted tetrahydropyrans, tetrahydrothiapyrans, piperidines, 1,3-dithianes, and 1,3-oxathianes [408], respectively. Methyl increments of these heterocycloalkanes are closely related to those derived for cyclohexane (Table 4.7) due to common structural features of six-membered rings. 

Murray, W.T., Kelly, J.W., and Evans, S.A., Jr., Synthesis of substituted 1,4-oxathianes, mechanistic details of diethoxytriphenylphosphorane — and triphenylphosphine/tetra-chloromethane — promoted cyclodehydrations and 13C NMR spectroscopy, J. Org. Chem., 52, 525, 1987. 

SCHEME 4.7 Generation of sulfonium ions using electrophilic aromatic substitution of oxathiane glycosyl donors. PTSA, p-toluenesulfonic acid. 

The stereochemistry of a few substituted 1,2-oxathianes 77-79, freshly synthesized (98TL1251), was studied (cf. Scheme 28) the conformation of the substituents at the six-membered ring is in agreement with NOE enhancements and the characteristic ax I ax vs. ax/equ and equ/equ vicinal... 

The stereochemistry, physical and chemical properties and some transformations of 1,3-oxathianes, especially alkyl substituent effects on the preferred conformers, were reviewed (99MI73, 00MI17). Also 1,3-oxathiane and its 2-substituted homologs were theoretically calculated using the semiempirical AMI and PM3 methods (98MI14) the experimental parameters are adequately reproduced. In the case of 5-alkyl substituted... 

Mercapto-l,3-diols are deprotonated at S by Et3N and in situ tosylation at S results in cyclisation through S-O bond formation, yielding substituted 1,2-oxathianes as a single diastereomer <02JCS(P1)2282>. 

The Cu-catalysed ring expansion of 2-substituted 1,3-oxathiolanes with ethyl (triethylsilyl)diazoacetate affords 2,3-disubstituted 1,4-oxathianes with variable diastereoselectivity the intermediacy of a Cu carbene and of a S-ylide is proposed <02CC346>. 

Acyclic 295 and cyclic 296 hemithioacetals have been shown as precursors of formyl-lithium intermediates13. For the preparation of the starting methoxy(phenylsulfanyl) methane 295466 two main procedures can be used (a) nucleophilic substitution of chloro-methyl methyl ether with thiophenol under basic conditions467,468 and (b) boron trifluoride etherate-catalyzed condensation of thiophenol and dimethoxymethane166. 1,3-Oxathiane and its derivatives can be prepared by acetalization of the corresponding carbonyl compound with 3-mercaptopropanol. 

The lithiation of 1,3-oxathiane (296) takes place with s-BuLi at —78 °C to give 2-lithio-1,3-oxathiane (315), an analogue of 2-lithio-l,3-dithiane (161), but with lower stability487. This intermediate reacts with different electrophiles, such as alkyl halides, carbonyl compounds, benzonitrile, dimethyl disulfide, dimethyl diselenide, trimethylplumbyl acetate and trimethylsilyl, germyl and stannyl chlorides488,489. However, further deprotection of 2-substituted 1,3-oxathianes has not been reported yet. 

Transetherification had earlier been employed to prepare thieno[3,4-3]-l,4-oxathiane 204 from 3,4-dimethoxythiophene <20020L607>. The difference in the reactivity of the 2- and 5- positions in 204 has been studied. Both monobromination and monoformylation gave the regioisomer substituted at the 5-position as the major product (Scheme 55). 

The commonly encountered C-2 anions derived from 1,3-dithiane and 1,3-oxathiane and their derivatives can be generated by treatment with any of a wide range of bases, but typically n-butyllithium (for 1,3-dithianes) or yec-butyllithium (sometimes necessary for 1,3-oxathianes). There are many instances where the deprotonated heterocycles have been used in synthesis, usually as acyl anion equivalents <8977643, b-95MI 608-05>. Use of 1,3-dithiane derivatives is by far the most common, and the derived anions react with with a very wide variety of electrophiles <69AG(E)639, 8977643), whether or not the dithiane system is initially substituted at C-2. For example, 2-lithio-... 

When deprotonation is effected in a 2-allyl-1,3-oxathiane with 5cc-butyllithium, the expected allylic anion is generated. Interestingly, reaction with alkyl halides leads to substitution at the a-terminus (52), whereas reaction with carbonyl compounds gives products of substitution at the y-terminus (53) (Scheme 18) <92TL250l>. In contrast, when the anion derived from 2-allyl-1,3-dithiane... 

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